chr12-119102244-C-T

Variant names:

• chr12-119102244-C-T
• rs182742763
• NM_194286.4:c.140C>T

Variant summary

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

The NM_194286.4(SRRM4):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,528 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (14 hom.)
• Consequence: SRRM4 NM_194286.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80
• Publications: 6 publications found

Genes affected

SRRM4 (HGNC:29389): (serine/arginine repetitive matrix 4) SRRM4 promotes alternative splicing and inclusion of neural-specific exons in target mRNAs (Calarco et al., 2009 [PubMed 19737518]).[supplied by OMIM, Oct 2009]

ENSG00000257095 (HGNC:58442):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004866749).
• BP6: Variant 12-119102244-C-T is Benign according to our data. Variant chr12-119102244-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3234197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194286.4. 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
	SRRM4	NM_194286.4	MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 2 of 13	NP_919262.2	A7MD48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM4	ENST00000267260.5	TSL:1 MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 2 of 13	ENSP00000267260.4	A7MD48
	SRRM4	ENST00000902270.1		c.140C>T	p.Pro47Leu	missense	Exon 2 of 12	ENSP00000572329.1
	ENSG00000257095	ENST00000537730.1	TSL:3	n.75+14643G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 152088 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000851

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00224 AC: 555 AN: 248220 AF XY: 0.00208

Gnomad AFR exome AF: 0.000582

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000651

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00516

GnomAD4 exome AF: 0.00356 AC: 5202 AN: 1460322 Hom.: 14 Cov.: 30 AF XY: 0.00335 AC XY: 2433 AN XY: 726494

African (AFR) AF: 0.000509 AC: 17 AN: 33414

American (AMR) AF: 0.00308 AC: 137 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86128

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00431 AC: 4794 AN: 1111186

Other (OTH) AF: 0.00314 AC: 189 AN: 60276

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152206 Hom.: 3 Cov.: 32 AF XY: 0.00198 AC XY: 147 AN XY: 74408

African (AFR) AF: 0.000674 AC: 28 AN: 41538

American (AMR) AF: 0.00537 AC: 82 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.000851 AC: 9 AN: 10582

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

European-Non Finnish (NFE) AF: 0.00373 AC: 254 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00314 Hom.: 3

Bravo AF: 0.00267

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00366 AC: 30

ExAC AF: 0.00230 AC: 278

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00295

EpiControl AF: 0.00346

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	0.073
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.035
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.045
Sift	Benign	0.58	T
Sift4G	Benign	0.38	T
Polyphen		0.073	B
Vest4		0.36
MVP		0.15
MPC		0.15
ClinPred		0.0094	T
GERP RS		3.9
Varity_R		0.067
gMVP		0.17
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs182742763; hg19: chr12-119540049;