rs552275462

Variant names:

• chr19-43612276-C-G
• rs552275462
• NM_001145641.2:c.155C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-43612276-C-G
• chr19-43612276-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145641.2(SRRM5):​c.155C>G​(p.Ser52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,551,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: SRRM5 NM_001145641.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.501
• Publications: 0 publications found

Genes affected

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023638368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145641.2. 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
	SRRM5	NM_001145641.2	MANE Select	c.155C>G	p.Ser52Cys	missense	Exon 1 of 1	NP_001139113.1	B3KS81
	ZNF428	NM_182498.4	MANE Select	c.76+1953G>C		intron	N/A	NP_872304.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM5	ENST00000417606.3	TSL:6 MANE Select	c.155C>G	p.Ser52Cys	missense	Exon 1 of 1	ENSP00000414512.1	B3KS81
	ZNF428	ENST00000300811.8	TSL:1 MANE Select	c.76+1953G>C		intron	N/A	ENSP00000300811.2	Q96B54
	SRRM5	ENST00000607544.1	TSL:2	c.155C>G	p.Ser52Cys	missense	Exon 3 of 3	ENSP00000476253.1	B3KS81

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000454 AC: 7 AN: 154138 AF XY: 0.0000489

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000642

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1399436 Hom.: 0 Cov.: 30 AF XY: 0.00000724 AC XY: 5 AN XY: 690234

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.000196 AC: 7 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078974

Other (OTH) AF: 0.0000172 AC: 1 AN: 58012

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74458

African (AFR) AF: 0.00 AC: 0 AN: 41570

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

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

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000413 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	0.14
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.50
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.060
Sift	Benign	0.043	D
Sift4G	Benign	0.070	T
Polyphen		0.99	D
Vest4		0.048
MutPred		0.16		Loss of phosphorylation at S52 (P = 0.0035)
MVP		0.040
MPC		0.066
ClinPred		0.15	T
GERP RS		2.4
PromoterAI		-0.0022	Neutral
Varity_R		0.064
gMVP		0.025
Mutation Taster		=100/0	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: rs552275462; hg19: chr19-44116428;