5-66596695-C-G

Variant names:

• chr5-66596695-C-G
• rs201236388
• NM_001164664.2:c.40C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001164664.2(MAST4):​c.40C>G​(p.Arg14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,471,582 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: MAST4 NM_001164664.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0170
• Publications: 4 publications found

Genes affected

MAST4 (HGNC:19037): (microtubule associated serine/threonine kinase family member 4) This gene encodes a member of the microtubule-associated serine/threonine protein kinases. The proteins in this family contain a domain that gives the kinase the ability to determine its own scaffold to control the effects of their kinase activities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012052506).
• BP6: Variant 5-66596695-C-G is Benign according to our data. Variant chr5-66596695-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 4280785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164664.2. 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
	MAST4	NM_001164664.2	MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 29	NP_001158136.1	O15021-5
	MAST4	NM_001393524.1		c.40C>G	p.Arg14Gly	missense	Exon 1 of 30	NP_001380453.1
	MAST4	NM_001393525.1		c.40C>G	p.Arg14Gly	missense	Exon 1 of 28	NP_001380454.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST4	ENST00000403625.7	TSL:5 MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 29	ENSP00000385727.1	O15021-5
	MAST4	ENST00000406374.5	TSL:1	c.40C>G	p.Arg14Gly	missense	Exon 1 of 6	ENSP00000385088.1	O15021-4
	MAST4	ENST00000406039.5	TSL:1	c.40C>G	p.Arg14Gly	missense	Exon 1 of 5	ENSP00000384547.1	E7EX28

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00154 AC: 206 AN: 133834 AF XY: 0.00136

Gnomad AFR exome AF: 0.000402

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.000610

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00253

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.000744

GnomAD4 exome AF: 0.00170 AC: 2241 AN: 1319394 Hom.: 3 Cov.: 33 AF XY: 0.00166 AC XY: 1082 AN XY: 651046

African (AFR) AF: 0.000406 AC: 11 AN: 27064

American (AMR) AF: 0.000114 AC: 3 AN: 26322

Ashkenazi Jewish (ASJ) AF: 0.000515 AC: 11 AN: 21374

East Asian (EAS) AF: 0.00 AC: 0 AN: 31362

South Asian (SAS) AF: 0.00 AC: 0 AN: 67270

European-Finnish (FIN) AF: 0.00305 AC: 129 AN: 42362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 0.00194 AC: 2032 AN: 1044984

Other (OTH) AF: 0.00103 AC: 55 AN: 53530

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74406

African (AFR) AF: 0.000289 AC: 12 AN: 41538

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.000790

ESP6500AA AF: 0.000304 AC: 1

ESP6500EA AF: 0.00133 AC: 10

ExAC AF: 0.00154 AC: 178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.017
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.033
Sift	Uncertain	0.011	D
Sift4G	Benign	0.091	T
Polyphen		0.46	P
Vest4		0.058
MVP		0.75
MPC		0.71
ClinPred		0.046	T
GERP RS		0.80
PromoterAI		0.0024	Neutral
Varity_R		0.093
gMVP		0.16
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs201236388; hg19: chr5-65892523; COSMIC: COSV105337508;