rs2967951

chr5-10463995-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047417967.1(LOC124900940):c.26C>T(p.Thr9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,144 control chromosomes in the GnomAD database, including 4,011 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (4011 hom., cov: 33)
• Consequence: LOC124900940 XM_047417967.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

LOC124900940 (HGNC:):

ROPN1L (HGNC:24060): (rhophilin associated tail protein 1 like) This gene encodes a member of the ropporin family. The encoded protein is present in sperm and interacts with A-kinase anchoring protein, AKAP3, through the amphipathic helix region of AKAP3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900940	XM_047417967.1	c.26C>T	p.Thr9Ile	missense_variant	1/1
ROPN1L	NM_031916.5	c.594-853C>T		intron_variant		ENST00000274134.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROPN1L	ENST00000274134.5	c.594-853C>T		intron_variant		1	NM_031916.5	P1
ROPN1L	ENST00000503804.5	c.594-853C>T		intron_variant		2		P1
ROPN1L	ENST00000510520.5	n.885+2636C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29226 AN: 152026 Hom.: 3987 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29295 AN: 152144 Hom.: 4011 Cov.: 33 AF XY: 0.200 AC XY: 14867 AN XY: 74388

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.189

Alfa AF: 0.134 Hom.: 2751

Bravo AF: 0.212

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.20
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs2967951; hg19: chr5-10464107;