9-123139551-G-A

Variant names:

• chr9-123139551-G-A
• rs1255898668
• NM_018387.5:c.1475C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_018387.5(STRBP):​c.1475C>T​(p.Thr492Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: STRBP NM_018387.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10500917).
• BS2: High AC in GnomAdExome4 at 5 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.1475C>T	p.Thr492Ile	missense	Exon 14 of 19	NP_060857.2
	STRBP	NM_001376106.1		c.1475C>T	p.Thr492Ile	missense	Exon 13 of 18	NP_001363035.1	Q96SI9-1
	STRBP	NM_001376107.1		c.1475C>T	p.Thr492Ile	missense	Exon 15 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.1475C>T	p.Thr492Ile	missense	Exon 14 of 19	ENSP00000321347.7	Q96SI9-1
	STRBP	ENST00000360998.3	TSL:1	c.1433C>T	p.Thr478Ile	missense	Exon 14 of 19	ENSP00000354271.3	Q96SI9-2
	STRBP	ENST00000407982.6	TSL:1	n.*1252C>T		non_coding_transcript_exon	Exon 14 of 19	ENSP00000384292.2	Q5JPA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248522 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459246 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725786

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 85708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111312

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.085
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.034
Sift	Benign	0.23	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.18		Loss of phosphorylation at T492 (P = 0.0697)
MVP		0.043
MPC		0.84
ClinPred		0.29	T
GERP RS		5.6
Varity_R		0.074
gMVP		0.27
Mutation Taster		=89/11	polymorphism

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: rs1255898668; hg19: chr9-125901830;