chr7-77736418-A-G

Position:

• chr7-77736418-A-G

Variant summary

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

The NM_198467.3(RSBN1L):​c.595A>G​(p.Lys199Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 915,816 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: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: RSBN1L NM_198467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

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]

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=0.20363557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1L	NM_198467.3	c.595A>G	p.Lys199Glu	missense_variant	2/8	ENST00000334955.13	NP_940869.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1L	ENST00000334955.13	c.595A>G	p.Lys199Glu	missense_variant	2/8	1	NM_198467.3	ENSP00000334040	P1
RSBN1L	ENST00000445288.5	c.-216A>G		5_prime_UTR_variant	2/8	5		ENSP00000393888

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 915816 Hom.: 0 Cov.: 12 AF XY: 0.00000218 AC XY: 1 AN XY: 457668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000351

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

Asia WGS AF: 0.00146 AC: 5 AN: 3442

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

Mar 07, 2023

The c.595A>G (p.K199E) alteration is located in exon 2 (coding exon 2) of the RSBN1L gene. This alteration results from a A to G substitution at nucleotide position 595, causing the lysine (K) at amino acid position 199 to be replaced by a glutamic acid (E). 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	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.080
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.29
MutPred		0.19		Loss of MoRF binding (P = 0.0029);
MVP		0.043
MPC		0.52
ClinPred		0.84	D
GERP RS		3.9
Varity_R		0.25
gMVP		0.13

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: rs369084586; hg19: chr7-77365735;