chr9-123132919-C-T

Variant names:

• chr9-123132919-C-T
• rs749670529
• NM_018387.5:c.1823G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018387.5(STRBP):​c.1823G>A​(p.Arg608Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,800 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: 0.0000014 (0 hom.)
• Consequence: STRBP NM_018387.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33646926).

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.1823G>A	p.Arg608Gln	missense	Exon 17 of 19	NP_060857.2
	STRBP	NM_001376106.1		c.1823G>A	p.Arg608Gln	missense	Exon 16 of 18	NP_001363035.1	Q96SI9-1
	STRBP	NM_001376107.1		c.1823G>A	p.Arg608Gln	missense	Exon 18 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.1823G>A	p.Arg608Gln	missense	Exon 17 of 19	ENSP00000321347.7	Q96SI9-1
	STRBP	ENST00000360998.3	TSL:1	c.1781G>A	p.Arg594Gln	missense	Exon 17 of 19	ENSP00000354271.3	Q96SI9-2
	STRBP	ENST00000407982.6	TSL:1	n.*1600G>A		non_coding_transcript_exon	Exon 17 of 19	ENSP00000384292.2	Q5JPA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251274 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461800 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.47		Loss of methylation at R608 (P = 0.0021)
MVP		0.15
MPC		1.6
ClinPred		0.89	D
GERP RS		6.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.67
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs749670529; hg19: chr9-125895198;