15-89472764-T-C

Variant names:

• chr15-89472764-T-C
• NM_016321.3:c.1411A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016321.3(RHCG):​c.1411A>G​(p.Met471Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RHCG NM_016321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.628

Genes affected

RHCG (HGNC:18140): (Rh family C glycoprotein) Enables ammonium transmembrane transporter activity; ankyrin binding activity; and identical protein binding activity. Involved in ammonium transmembrane transport; cellular ion homeostasis; and transepithelial ammonium transport. Located in apical plasma membrane and basolateral plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05319205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHCG	NM_016321.3	c.1411A>G	p.Met471Val	missense_variant	Exon 10 of 11	ENST00000268122.9	NP_057405.1
RHCG	NM_001321041.2	c.1411A>G	p.Met471Val	missense_variant	Exon 10 of 11		NP_001307970.1
RHCG	XM_047432651.1	c.1411A>G	p.Met471Val	missense_variant	Exon 10 of 11		XP_047288607.1
RHCG	NR_110261.2	n.1374A>G		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHCG	ENST00000268122.9	c.1411A>G	p.Met471Val	missense_variant	Exon 10 of 11	1	NM_016321.3	ENSP00000268122.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1411A>G (p.M471V) alteration is located in exon 10 (coding exon 10) of the RHCG gene. This alteration results from a A to G substitution at nucleotide position 1411, causing the methionine (M) at amino acid position 471 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
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.4
DANN	Benign	0.39
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.030
Sift	Benign	0.32	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.17		Gain of catalytic residue at M471 (P = 0.0044);
MVP		0.055
MPC		0.21
ClinPred		0.24	T
GERP RS		-2.4
Varity_R		0.044
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr15-90015995;