rs780402725

Variant names:

• chr21-29149238-C-A
• rs780402725
• NM_001286620.2:c.120C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-29149238-C-A
• chr21-29149238-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001286620.2(MAP3K7CL):​c.120C>A​(p.Asp40Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,600 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (1 hom.)
• Consequence: MAP3K7CL NM_001286620.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0950
• Publications: 0 publications found

Genes affected

MAP3K7CL (HGNC:16457): (MAP3K7 C-terminal like) Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03475693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7CL	NM_001286620.2	c.120C>A	p.Asp40Glu	missense_variant	Exon 3 of 5	ENST00000399928.6	NP_001273549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7CL	ENST00000399928.6	c.120C>A	p.Asp40Glu	missense_variant	Exon 3 of 5	1	NM_001286620.2	ENSP00000382812.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251336 AF XY: 0.0000368

Gnomad AFR exome AF: 0.0000615

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: 0.0000219 AC: 32 AN: 1461406 Hom.: 1 Cov.: 29 AF XY: 0.0000358 AC XY: 26 AN XY: 727048

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111582

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000494 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.420C>A (p.D140E) alteration is located in exon 7 (coding exon 5) of the MAP3K7CL gene. This alteration results from a C to A substitution at nucleotide position 420, causing the aspartic acid (D) at amino acid position 140 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T;.;.;T;T;.;.;.;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.70	.;.;.;.;T;.;T;.;.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.035	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.;N;N;.;.;.;.;.;.
PhyloP100		-0.095
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N;N;N;N;.;N;N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.43	T;T;T;T;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.096	B;.;.;B;B;.;.;.;.;.;.
Vest4		0.31
MutPred		0.32		Gain of helix (P = 0.132);.;.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;.;.;.;.;
MVP		0.12
MPC		0.40
ClinPred		0.045	T
GERP RS		0.41
Varity_R		0.056
gMVP		0.098
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780402725; hg19: chr21-30521559;