9-123159156-C-T

Variant names:

• chr9-123159156-C-T
• rs2037415298
• NM_018387.5:c.775G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018387.5(STRBP):​c.775G>A​(p.Gly259Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,374 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: STRBP NM_018387.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2933299).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018387.5. 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
	STRBP	NM_018387.5	MANE Select	c.775G>A	p.Gly259Ser	missense	Exon 9 of 19	NP_060857.2
	STRBP	NM_001376106.1		c.775G>A	p.Gly259Ser	missense	Exon 8 of 18	NP_001363035.1	Q96SI9-1
	STRBP	NM_001376107.1		c.775G>A	p.Gly259Ser	missense	Exon 10 of 20	NP_001363036.1	Q96SI9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRBP	ENST00000348403.10	TSL:1 MANE Select	c.775G>A	p.Gly259Ser	missense	Exon 9 of 19	ENSP00000321347.7	Q96SI9-1
	STRBP	ENST00000360998.3	TSL:1	c.733G>A	p.Gly245Ser	missense	Exon 9 of 19	ENSP00000354271.3	Q96SI9-2
	STRBP	ENST00000407982.6	TSL:1	n.*552G>A		non_coding_transcript_exon	Exon 9 of 19	ENSP00000384292.2	Q5JPA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461374 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726982

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111624

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.67	N
PhyloP100		6.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.33
Sift	Benign	0.50	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.37
MVP		0.20
MPC		1.9
ClinPred		0.94	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.78
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2037415298; hg19: chr9-125921435;