15-40038428-C-T

Variant names:

• chr15-40038428-C-T
• rs8041057
• NM_003134.6:c.98-34G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003134.6(SRP14):​c.98-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,451,416 control chromosomes in the GnomAD database, including 329,760 homozygotes. 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: 𝑓 0.58 (27389 hom., cov: 32)
  • Exomes 𝑓: 0.67 (302371 hom.)
• Consequence: SRP14 NM_003134.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 34 publications found

Genes affected

SRP14 (HGNC:11299): (signal recognition particle 14) Enables RNA binding activity. Involved in protein targeting to ER. Located in nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903471 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP14	NM_003134.6	c.98-34G>A		intron_variant	Intron 2 of 4	ENST00000267884.11	NP_003125.3
SRP14	NM_001309434.1	c.-87-34G>A		intron_variant	Intron 2 of 5		NP_001296363.1
LOC124903471	XR_007064596.1	n.*19C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP14	ENST00000267884.11	c.98-34G>A		intron_variant	Intron 2 of 4	1	NM_003134.6	ENSP00000267884.6

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87560 AN: 151856 Hom.: 27386 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.604

GnomAD2 exomes AF: 0.606 AC: 150439 AN: 248438 AF XY: 0.620

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.714

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.673 AC: 874899 AN: 1299442 Hom.: 302371 Cov.: 19 AF XY: 0.674 AC XY: 441976 AN XY: 655358

African (AFR) AF: 0.348 AC: 10499 AN: 30130

American (AMR) AF: 0.458 AC: 20369 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 17656 AN: 25158

East Asian (EAS) AF: 0.275 AC: 10723 AN: 39036

South Asian (SAS) AF: 0.625 AC: 51848 AN: 83014

European-Finnish (FIN) AF: 0.683 AC: 36251 AN: 53114

Middle Eastern (MID) AF: 0.670 AC: 3662 AN: 5462

European-Non Finnish (NFE) AF: 0.714 AC: 688287 AN: 963870

Other (OTH) AF: 0.645 AC: 35604 AN: 55224

GnomAD4 genome AF: 0.576 AC: 87576 AN: 151974 Hom.: 27389 Cov.: 32 AF XY: 0.573 AC XY: 42534 AN XY: 74264

African (AFR) AF: 0.355 AC: 14714 AN: 41424

American (AMR) AF: 0.521 AC: 7962 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2441 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5162

South Asian (SAS) AF: 0.622 AC: 3000 AN: 4820

European-Finnish (FIN) AF: 0.673 AC: 7099 AN: 10544

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48780 AN: 67964

Other (OTH) AF: 0.603 AC: 1269 AN: 2106

Alfa AF: 0.662 Hom.: 125434

Bravo AF: 0.551

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs8041057; hg19: chr15-40330629; COSMIC: COSV51115462; COSMIC: COSV51115462;