1-42830860-C-T

Variant names:

• chr1-42830860-C-T
• rs56136737
• NM_001017922.2:c.178C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062319756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	NM_001017922.2	MANE Select	c.178C>T	p.Pro60Ser	missense	Exon 4 of 12	NP_001017922.1
	ERMAP	NM_018538.4		c.178C>T	p.Pro60Ser	missense	Exon 3 of 11	NP_061008.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	ENST00000372517.8	TSL:1 MANE Select	c.178C>T	p.Pro60Ser	missense	Exon 4 of 12	ENSP00000361595.2
	ERMAP	ENST00000372514.7	TSL:1	c.178C>T	p.Pro60Ser	missense	Exon 3 of 11	ENSP00000361592.3
	ERMAP	ENST00000328249.3	TSL:1	n.946C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244722 AF XY: 0.00000756

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: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110650

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.038
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.012
Sift	Benign	0.41	T
Sift4G	Benign	0.88	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.42		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
Mutation Taster		=98/2	polymorphism

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: rs56136737; hg19: chr1-43296531;