chr1-42830860-C-T

Position:

• chr1-42830860-C-T

Variant summary

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

The NM_001017922.2(ERMAP):​c.178C>T​(p.Pro60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. P60A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ERMAP NM_001017922.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

Genes affected

ERMAP (HGNC:15743): (erythroblast membrane associated protein (Scianna blood group)) The protein encoded by this gene is a cell surface transmembrane protein that may act as an erythroid cell receptor, possibly as a mediator of cell adhesion. Polymorphisms in this gene are responsible for the Scianna/Radin blood group system. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ERMAP (HGNC:):

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=0.062319756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERMAP	NM_001017922.2	c.178C>T	p.Pro60Ser	missense_variant	4/12	ENST00000372517.8	NP_001017922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERMAP	ENST00000372517.8	c.178C>T	p.Pro60Ser	missense_variant	4/12	1	NM_001017922.2	ENSP00000361595.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244722 Hom.: 0 AF XY: 0.00000756 AC XY: 1 AN XY: 132268

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 SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458844 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0019	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.012
Sift	Benign	0.41	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.0020	B;B
Vest4		0.17
MutPred		0.42		Gain of MoRF binding (P = 0.0474);Gain of MoRF binding (P = 0.0474);
MVP		0.10
MPC		0.15
ClinPred		0.053	T
GERP RS		0.30
Varity_R		0.050
gMVP		0.39

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: rs56136737; hg19: chr1-43296531;