chr5-154446660-C-T

Variant names:

• chr5-154446660-C-T
• rs774022587
• NM_024632.6:c.56C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024632.6(SAP30L):​c.56C>T​(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,545,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SAP30L NM_024632.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.210
• Publications: 0 publications found

Genes affected

SAP30L (HGNC:25663): (SAP30 like) Enables several functions, including non-sequence-specific DNA binding activity, bending; phosphatidylinositol phosphate binding activity; and zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. Part of histone deacetylase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07045075).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024632.6. 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
	SAP30L	NM_024632.6	MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 4	NP_078908.1	Q9HAJ7-1
	SAP30L	NM_001131062.2		c.56C>T	p.Ala19Val	missense	Exon 1 of 3	NP_001124534.1	Q9HAJ7-3
	SAP30L	NM_001131063.2		c.56C>T	p.Ala19Val	missense	Exon 1 of 3	NP_001124535.1	Q9HAJ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP30L	ENST00000297109.11	TSL:1 MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 4	ENSP00000297109.5	Q9HAJ7-1
	SAP30L	ENST00000937072.1		c.56C>T	p.Ala19Val	missense	Exon 1 of 5	ENSP00000607131.1
	SAP30L	ENST00000960937.1		c.56C>T	p.Ala19Val	missense	Exon 1 of 4	ENSP00000630996.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000211 AC: 3 AN: 141862 AF XY: 0.0000254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000537

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 163 AN: 1393296 Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 73 AN XY: 688484

African (AFR) AF: 0.0000984 AC: 3 AN: 30482

American (AMR) AF: 0.00 AC: 0 AN: 35828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24808

East Asian (EAS) AF: 0.00 AC: 0 AN: 35288

South Asian (SAS) AF: 0.00 AC: 0 AN: 79506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.000139 AC: 150 AN: 1081158

Other (OTH) AF: 0.000173 AC: 10 AN: 57960

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.0000482 AC: 2 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00000929 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.21
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.020
Sift	Benign	0.18	T
Sift4G	Benign	0.24	T
Polyphen		0.90	P
Vest4		0.12
MutPred		0.22		Loss of glycosylation at P18 (P = 0.0539)
MVP		0.10
MPC		0.54
ClinPred		0.029	T
GERP RS		0.16
PromoterAI		0.015	Neutral
Varity_R		0.088
gMVP		0.21
Mutation Taster		=95/5	polymorphism

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: rs774022587; hg19: chr5-153826220;