chr7-156643888-A-T

Position:

• chr7-156643888-A-T

Variant summary

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

The NM_030936.4(RNF32):​c.11A>T​(p.Asn4Ile) 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. 12/21 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: RNF32 NM_030936.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

Genes affected

RNF32 (HGNC:17118): (ring finger protein 32) The protein encoded by this gene contains two RING ring finger motifs. RING finger motifs are present in a variety of functionally distinct proteins and are known to be involved in protein-DNA or protein-protein interactions. This gene was found to be expressed during spermatogenesis, most likely in spermatocytes and/or in spermatids. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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=0.16293168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF32	NM_030936.4	c.11A>T	p.Asn4Ile	missense_variant	2/9	ENST00000317955.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF32	ENST00000317955.10	c.11A>T	p.Asn4Ile	missense_variant	2/9	1	NM_030936.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

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

Jul 27, 2023

The c.11A>T (p.N4I) alteration is located in exon 2 (coding exon 1) of the RNF32 gene. This alteration results from a A to T substitution at nucleotide position 11, causing the asparagine (N) at amino acid position 4 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.60	T;.;.;.;.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	0.77	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D;D;D
REVEL	Benign	0.089
Sift	Uncertain	0.012	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.017	D;.;D;D;D;D;D;D
Polyphen		0.38, 0.43, 0.32	.;.;B;B;B;B;B;B
Vest4		0.32, 0.29, 0.29, 0.30, 0.32
MutPred		0.33		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.73
MPC		0.19
ClinPred		0.34	T
GERP RS		2.1
Varity_R		0.18
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-156436582;