SRRM3 p.Phe22Leu

Variant names:

• chr7-76235132-C-A
• NM_001110199.3:c.66C>A
• SRRM3 p.Phe22Leu

Your query was ambiguous. Multiple possible variants found:

• chr7-76235132-C-A
• chr7-76235132-C-G
• chr7-76235130-T-C
• chr7-76235130-TTC-CTT
• chr7-76235130-TTC-CTA
• chr7-76235130-TTC-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001110199.3(SRRM3):​c.66C>A​(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. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SRRM3 NM_001110199.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08034298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110199.3. 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
	SRRM3	NM_001110199.3	MANE Select	c.66C>A	p.Phe22Leu	missense	Exon 2 of 15	NP_001103669.1	A0A087WXA3
	SRRM3	NM_001291831.2		c.66C>A	p.Phe22Leu	missense	Exon 2 of 16	NP_001278760.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM3	ENST00000611745.2	TSL:5 MANE Select	c.66C>A	p.Phe22Leu	missense	Exon 2 of 15	ENSP00000480851.1	A0A087WXA3
	SRRM3	ENST00000479294.2	TSL:2	n.151C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1419238 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 703856

African (AFR) AF: 0.00 AC: 0 AN: 32328

American (AMR) AF: 0.00 AC: 0 AN: 39812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 37550

South Asian (SAS) AF: 0.00 AC: 0 AN: 81776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098014

Other (OTH) AF: 0.00 AC: 0 AN: 58944

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.53
PrimateAI	Pathogenic	0.83	D
Sift4G	Benign	0.37	T
gMVP		0.81
Mutation Taster		=92/8	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-75864450;