Variant 9-123132869-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_018387.5(STRBP):c.1873G>C(p.Ala625Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Consequence

STRBP
NM_018387.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

STRBP (HGNC:16462): (spermatid perinuclear RNA binding protein) Enables RNA binding activity. Predicted to be involved in spermatogenesis. Predicted to act upstream of or within mechanosensory behavior and spermatid development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STRBP links:

STRBP (HGNC:):

STRBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24945459).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRBP	NM_018387.5 linkuse as main transcript	c.1873G>C	p.Ala625Pro	missense_variant	17/19	ENST00000348403.10	NP_060857.2	Q96SI9-1V9HWK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRBP	ENST00000348403.10 linkuse as main transcript	c.1873G>C	p.Ala625Pro	missense_variant	17/19	1	NM_018387.5	ENSP00000321347.7		Q96SI9-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251136

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.1873G>C (p.A625P) alteration is located in exon 1 (coding exon 1) of the STRBP gene. This alteration results from a G to C substitution at nucleotide position 1873, causing the alanine (A) at amino acid position 625 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.97

L;L;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.060

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.84

P;P;D

Vest4

0.43

MutPred

0.51

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;

MVP

0.20

MPC

1.0

ClinPred

0.27

GERP RS

6.0

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.15

gMVP

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over