NM_138785.5:c.262T>C

Variant names:

• chr6-149572588-T-C
• rs765049479
• NM_138785.5:c.262T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138785.5(GINM1):​c.262T>C​(p.Cys88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C88G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GINM1 NM_138785.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• Publications: 0 publications found

Genes affected

GINM1 (HGNC:21074): (glycosylated integral membrane protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GINM1	NM_138785.5	c.262T>C	p.Cys88Arg	missense_variant	Exon 3 of 8	ENST00000367419.10	NP_620140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINM1	ENST00000367419.10	c.262T>C	p.Cys88Arg	missense_variant	Exon 3 of 8	1	NM_138785.5	ENSP00000356389.5
GINM1	ENST00000650599.1	n.262T>C		non_coding_transcript_exon_variant	Exon 3 of 8			ENSP00000496902.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249528 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424130 Hom.: 0 Cov.: 24 AF XY: 0.00000281 AC XY: 2 AN XY: 710894

African (AFR) AF: 0.00 AC: 0 AN: 32646

American (AMR) AF: 0.00 AC: 0 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39516

South Asian (SAS) AF: 0.00 AC: 0 AN: 85152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078746

Other (OTH) AF: 0.00 AC: 0 AN: 59050

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0070	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.93	P
Vest4		0.89
MutPred		0.67		Gain of MoRF binding (P = 0.0275);
MVP		0.61
MPC		1.1
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.90
gMVP		0.75
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs765049479; hg19: chr6-149893724;