7-77696858-T-A

Position:

• chr7-77696858-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198467.3(RSBN1L):​c.389T>A​(p.Val130Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSBN1L NM_198467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.371

Genes affected

RSBN1L (HGNC:24765): (round spermatid basic protein 1 like) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

APTR (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22113994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1L	NM_198467.3	c.389T>A	p.Val130Asp	missense_variant	1/8	ENST00000334955.13	NP_940869.2
APTR	NR_038361.1	n.488A>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1L	ENST00000334955.13	c.389T>A	p.Val130Asp	missense_variant	1/8	1	NM_198467.3	ENSP00000334040.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 21, 2024

The c.389T>A (p.V130D) alteration is located in exon 1 (coding exon 1) of the RSBN1L gene. This alteration results from a T to A substitution at nucleotide position 389, causing the valine (V) at amino acid position 130 to be replaced by an aspartic acid (D). 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	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.061	T
Polyphen		0.97	D
Vest4		0.43
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.082
MPC		0.71
ClinPred		0.88	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.47

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

Other links and lift over

dbSNP: rs1790737989; hg19: chr7-77326175;