9-123161047-G-A

Position:

• chr9-123161047-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018387.5(STRBP):​c.557C>T​(p.Pro186Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: STRBP NM_018387.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRBP	NM_018387.5	c.557C>T	p.Pro186Leu	missense_variant	7/19	ENST00000348403.10	NP_060857.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRBP	ENST00000348403.10	c.557C>T	p.Pro186Leu	missense_variant	7/19	1	NM_018387.5	ENSP00000321347.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448382 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720354

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

The c.557C>T (p.P186L) alteration is located in exon 1 (coding exon 1) of the STRBP gene. This alteration results from a C to T substitution at nucleotide position 557, causing the proline (P) at amino acid position 186 to be replaced by a leucine (L). 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	0.30
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;D;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-8.0	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.097	T;T;T
Polyphen		0.020	B;B;.
Vest4		0.56
MutPred		0.81		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;
MVP		0.44
MPC		0.85
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-125923326;