rs7535

Variant names:

• chr15-40036374-G-C
• rs7535
• NM_003134.6:c.370C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40036374-G-C
• chr15-40036374-G-A
• chr15-40036374-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003134.6(SRP14):​c.370C>G​(p.Pro124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,612,888 control chromosomes in the GnomAD database, including 669,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61516 hom., cov: 35)
  • Exomes 𝑓: 0.91 (608307 hom.)
• Consequence: SRP14 NM_003134.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.715
• Publications: 33 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.785058E-7).
• BP6: Variant 15-40036374-G-C is Benign according to our data. Variant chr15-40036374-G-C is described in ClinVar as Benign. ClinVar VariationId is 402822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003134.6. 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
	SRP14	NM_003134.6	MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 5 of 5	NP_003125.3
	SRP14	NM_001309434.1		c.226C>G	p.Pro76Ala	missense	Exon 6 of 6	NP_001296363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP14	ENST00000267884.11	TSL:1 MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 5 of 5	ENSP00000267884.6	P37108
	SRP14	ENST00000922619.1		c.436C>G	p.Pro146Ala	missense	Exon 5 of 5	ENSP00000592678.1
	SRP14	ENST00000922618.1		c.202C>G	p.Pro68Ala	missense	Exon 3 of 3	ENSP00000592677.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136680 AN: 151990 Hom.: 61479 Cov.: 35

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.905

GnomAD2 exomes AF: 0.904 AC: 227301 AN: 251320 AF XY: 0.904

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.960

Gnomad ASJ exome AF: 0.869

Gnomad EAS exome AF: 0.759

Gnomad FIN exome AF: 0.908

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.912

GnomAD4 exome AF: 0.912 AC: 1332618 AN: 1460782 Hom.: 608307 Cov.: 63 AF XY: 0.912 AC XY: 662410 AN XY: 726690

African (AFR) AF: 0.861 AC: 28772 AN: 33418

American (AMR) AF: 0.958 AC: 42834 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 22732 AN: 26018

East Asian (EAS) AF: 0.753 AC: 29808 AN: 39610

South Asian (SAS) AF: 0.895 AC: 77145 AN: 86160

European-Finnish (FIN) AF: 0.908 AC: 48493 AN: 53408

Middle Eastern (MID) AF: 0.896 AC: 5119 AN: 5710

European-Non Finnish (NFE) AF: 0.921 AC: 1023733 AN: 1111402

Other (OTH) AF: 0.895 AC: 53982 AN: 60348

GnomAD4 genome AF: 0.899 AC: 136772 AN: 152106 Hom.: 61516 Cov.: 35 AF XY: 0.897 AC XY: 66712 AN XY: 74360

African (AFR) AF: 0.861 AC: 35701 AN: 41474

American (AMR) AF: 0.936 AC: 14306 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3060 AN: 3454

East Asian (EAS) AF: 0.768 AC: 3945 AN: 5140

South Asian (SAS) AF: 0.902 AC: 4346 AN: 4818

European-Finnish (FIN) AF: 0.904 AC: 9588 AN: 10612

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62792 AN: 68004

Other (OTH) AF: 0.905 AC: 1906 AN: 2106

Alfa AF: 0.916 Hom.: 10170

Bravo AF: 0.899

TwinsUK AF: 0.921 AC: 3414

ALSPAC AF: 0.917 AC: 3533

ESP6500AA AF: 0.873 AC: 3845

ESP6500EA AF: 0.926 AC: 7966

ExAC AF: 0.904 AC: 109692

Asia WGS AF: 0.826 AC: 2874 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.0
DANN	Benign	0.34
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.71
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.060
MPC		0.49
ClinPred		0.00092	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.084
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: rs7535; hg19: chr15-40328575; COSMIC: COSV51115776; COSMIC: COSV51115776;