chr7-76235132-C-G

Variant names:

• chr7-76235132-C-G
• NM_001110199.3:c.66C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001110199.3(SRRM3):​c.66C>G​(p.Phe22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRM3 NM_001110199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.534

Genes affected

SRRM3 (HGNC:26729): (serine/arginine repetitive matrix 3) Predicted to enable mRNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07999566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRM3	NM_001110199.3	c.66C>G	p.Phe22Leu	missense_variant	Exon 2 of 15	ENST00000611745.2	NP_001103669.1
SRRM3	NM_001291831.2	c.66C>G	p.Phe22Leu	missense_variant	Exon 2 of 16		NP_001278760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRM3	ENST00000611745.2	c.66C>G	p.Phe22Leu	missense_variant	Exon 2 of 15	5	NM_001110199.3	ENSP00000480851.1
SRRM3	ENST00000479294.2	n.151C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.66C>G (p.F22L) alteration is located in exon 2 (coding exon 1) of the SRRM3 gene. This alteration results from a C to G substitution at nucleotide position 66, causing the phenylalanine (F) at amino acid position 22 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
PrimateAI	Pathogenic	0.83	D
Sift4G	Benign	0.37	T
Vest4		0.16
MutPred		0.24		Gain of glycosylation at S26 (P = 0.1342);
MVP		0.043
ClinPred		0.18	T
GERP RS		2.8
gMVP		0.81

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-75864450;