rs3802526

Variant names:

• chr10-27170817-C-G
• rs3802526
• NM_001172303.3:c.1858C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-27170817-C-G
• chr10-27170817-C-A
• chr10-27170817-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001172303.3(MASTL):​c.1858C>G​(p.Pro620Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 1,613,964 control chromosomes in the GnomAD database, including 4,616 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (474 hom., cov: 32)
  • Exomes 𝑓: 0.064 (4142 hom.)
• Consequence: MASTL NM_001172303.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.331
• Publications: 21 publications found

Genes affected

MASTL (HGNC:19042): (microtubule associated serine/threonine kinase like) This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]

ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACBD5 Gene-Disease associations (from GenCC):

• acyl-CoA binding domain containing protein 5 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinal dystrophy with leukodystrophy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017546713).
• BP6: Variant 10-27170817-C-G is Benign according to our data. Variant chr10-27170817-C-G is described in ClinVar as Benign. ClinVar VariationId is 262116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172303.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	NM_001172303.3	MANE Select	c.1858C>G	p.Pro620Ala	missense	Exon 8 of 12	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.1858C>G	p.Pro620Ala	missense	Exon 8 of 13	NP_001307686.1
	MASTL	NM_001320756.2		c.1858C>G	p.Pro620Ala	missense	Exon 8 of 13	NP_001307685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.1858C>G	p.Pro620Ala	missense	Exon 8 of 12	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.1858C>G	p.Pro620Ala	missense	Exon 8 of 12	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.1858C>G	p.Pro620Ala	missense	Exon 8 of 13	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11108 AN: 152078 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.0821 AC: 20620 AN: 251038 AF XY: 0.0842

Gnomad AFR exome AF: 0.0854

Gnomad AMR exome AF: 0.0657

Gnomad ASJ exome AF: 0.0729

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0548

Gnomad OTH exome AF: 0.0675

GnomAD4 exome AF: 0.0644 AC: 94112 AN: 1461768 Hom.: 4142 Cov.: 34 AF XY: 0.0667 AC XY: 48502 AN XY: 727188

African (AFR) AF: 0.0869 AC: 2910 AN: 33478

American (AMR) AF: 0.0623 AC: 2785 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 1921 AN: 26132

East Asian (EAS) AF: 0.206 AC: 8162 AN: 39678

South Asian (SAS) AF: 0.144 AC: 12397 AN: 86256

European-Finnish (FIN) AF: 0.109 AC: 5809 AN: 53412

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5768

European-Non Finnish (NFE) AF: 0.0502 AC: 55802 AN: 1111934

Other (OTH) AF: 0.0669 AC: 4040 AN: 60390

GnomAD4 genome AF: 0.0731 AC: 11124 AN: 152196 Hom.: 474 Cov.: 32 AF XY: 0.0772 AC XY: 5744 AN XY: 74408

African (AFR) AF: 0.0852 AC: 3539 AN: 41544

American (AMR) AF: 0.0507 AC: 775 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0773 AC: 268 AN: 3466

East Asian (EAS) AF: 0.160 AC: 827 AN: 5162

South Asian (SAS) AF: 0.156 AC: 752 AN: 4834

European-Finnish (FIN) AF: 0.108 AC: 1139 AN: 10584

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0541 AC: 3681 AN: 67996

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0597 Hom.: 279

Bravo AF: 0.0689

TwinsUK AF: 0.0539 AC: 200

ALSPAC AF: 0.0485 AC: 187

ESP6500AA AF: 0.0819 AC: 361

ESP6500EA AF: 0.0522 AC: 449

ExAC AF: 0.0840 AC: 10204

Asia WGS AF: 0.154 AC: 533 AN: 3478

EpiCase AF: 0.0528

EpiControl AF: 0.0499

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.1
DANN	Benign	0.75
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.33
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.063
Sift	Benign	0.18	T
Sift4G	Benign	0.49	T
Polyphen		0.29	B
Vest4		0.16
MPC		0.15
ClinPred		0.017	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.12
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3802526; hg19: chr10-27459746; COSMIC: COSV60909850;