chrX-38160997-G-T

Variant names:

• chrX-38160997-G-T
• rs374069621
• NM_006307.5:c.711C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006307.5(SRPX):​c.711C>A​(p.Ile237Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,428 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: SRPX NM_006307.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

Genes affected

SRPX (HGNC:11309): (sushi repeat containing protein X-linked) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of cell proliferation involved in contact inhibition; phagolysosome assembly; and positive regulation of extrinsic apoptotic signaling pathway in absence of ligand. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006307.5. 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
	SRPX	NM_006307.5	MANE Select	c.711C>A	p.Ile237Ile	synonymous	Exon 6 of 10	NP_006298.1	P78539-1
	SRPX	NM_001170750.2		c.651C>A	p.Ile217Ile	synonymous	Exon 5 of 9	NP_001164221.1	P78539-5
	SRPX	NM_001170751.2		c.534C>A	p.Ile178Ile	synonymous	Exon 5 of 9	NP_001164222.1	P78539-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX	ENST00000378533.4	TSL:1 MANE Select	c.711C>A	p.Ile237Ile	synonymous	Exon 6 of 10	ENSP00000367794.3	P78539-1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-505124G>T		intron	N/A	ENSP00000417050.1	B4E171
	SRPX	ENST00000898757.1		c.711C>A	p.Ile237Ile	synonymous	Exon 6 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097428 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1 AN XY: 362820

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4023

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841652

Other (OTH) AF: 0.00 AC: 0 AN: 46055

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		2.3

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: rs374069621; hg19: chrX-38020250;