1-156377342-T-G

Position:

• chr1-156377342-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020407.5(RHBG):​c.229T>G​(p.Phe77Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHBG NM_020407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

Genes affected

RHBG (HGNC:14572): (Rh family B glycoprotein) This gene encodes one of two non-erythroid members of the Rhesus (Rh) protein family. Non-erythroid Rh protein family members are mainly expressed in the kidney and belong to the methylammonium-ammonium permease/ammonia transporters superfamily. All Rh family proteins are predicted to be transmembrane proteins with 12 membrane spanning domains and intracytoplasmic N- and C-termini. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBG	NM_020407.5	c.229T>G	p.Phe77Val	missense_variant	2/10	ENST00000537040.6	NP_065140.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBG	ENST00000537040.6	c.229T>G	p.Phe77Val	missense_variant	2/10	1	NM_020407.5	ENSP00000441197	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 16, 2021

The c.229T>G (p.F77V) alteration is located in exon 2 (coding exon 2) of the RHBG gene. This alteration results from a T to G substitution at nucleotide position 229, causing the phenylalanine (F) at amino acid position 77 to be replaced by a valine (V). 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
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.63	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.71
MutPred		0.78		Loss of helix (P = 0.2662);
MVP		0.76
ClinPred		0.96	D
GERP RS		4.9
gMVP		0.89

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: rs1667279562; hg19: chr1-156347133;