chr1-23971864-C-T

Variant names:

• chr1-23971864-C-T
• rs112665933
• NM_054016.4:c.423G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_054016.4(SRSF10):​c.423G>A​(p.Ser141Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,607,270 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: SRSF10 NM_054016.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.139
• Publications: 0 publications found

Genes affected

SRSF10 (HGNC:16713): (serine and arginine rich splicing factor 10) This gene product is a member of the serine-arginine (SR) family of proteins, which are involved in constitutive and regulated RNA splicing. Members of this family are characterized by N-terminal RNP1 and RNP2 motifs, which are required for binding to RNA, and multiple C-terminal SR/RS repeats, which are important in mediating association with other cellular proteins. This protein interacts with the oncoprotein TLS, and abrogates the influence of TLS on adenovirus E1A pre-mRNA splicing. This gene has pseudogenes on chromosomes 4, 9, 14, 18, and 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-23971864-C-T is Benign according to our data. Variant chr1-23971864-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.
• BS2: High AC in GnomAd4 at 319 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054016.4. 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
	SRSF10	NM_054016.4	MANE Select	c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 6	NP_473357.1	O75494-1
	SRSF10	NM_001191005.3		c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 6	NP_001177934.1	O75494-2
	SRSF10	NM_001300937.2		c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 7	NP_001287866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF10	ENST00000492112.3	TSL:1 MANE Select	c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 6	ENSP00000420195.1	O75494-1
	SRSF10	ENST00000343255.9	TSL:2	c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 6	ENSP00000344149.4	O75494-2
	SRSF10	ENST00000344989.10	TSL:1	c.423G>A	p.Ser141Ser	synonymous	Exon 4 of 6	ENSP00000342913.5	O75494-3

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152132 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000827 AC: 24 AN: 29018 AF XY: 0.000825

Gnomad AFR exome AF: 0.00618

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.000247 AC: 359 AN: 1455020 Hom.: 1 Cov.: 31 AF XY: 0.000207 AC XY: 150 AN XY: 723896

African (AFR) AF: 0.00589 AC: 194 AN: 32924

American (AMR) AF: 0.000798 AC: 34 AN: 42580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39592

South Asian (SAS) AF: 0.0000471 AC: 4 AN: 84918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5732

European-Non Finnish (NFE) AF: 0.0000550 AC: 61 AN: 1110042

Other (OTH) AF: 0.000982 AC: 59 AN: 60106

GnomAD4 genome AF: 0.00210 AC: 319 AN: 152250 Hom.: 2 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74438

African (AFR) AF: 0.00657 AC: 273 AN: 41546

American (AMR) AF: 0.00249 AC: 38 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68004

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.00233

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
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.5
DANN	Benign	0.73
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs112665933; hg19: chr1-24298354;