ENST00000341618.8:c.358A>T

Variant names:

• chr21-29092569-A-T
• rs757578574
• ENST00000341618.8:c.358A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000341618.8(MAP3K7CL):​c.358A>T​(p.Ser120Cys) 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. 13/21 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. S120G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP3K7CL ENST00000341618.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1983721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7CL	NM_001286617.2	c.-181A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 5 of 10		NP_001273546.1
MAP3K7CL	NM_001286618.2	c.-52A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 5 of 9		NP_001273547.1
MAP3K7CL	NM_001286619.2	c.-325A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7		NP_001273548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7CL	ENST00000341618.8	c.358A>T	p.Ser120Cys	missense_variant	Exon 5 of 8	1		ENSP00000343212.4
MAP3K7CL	ENST00000399947.6	c.358A>T	p.Ser120Cys	missense_variant	Exon 6 of 9	1		ENSP00000382828.2
MAP3K7CL	ENST00000496779.5	n.806A>T		non_coding_transcript_exon_variant	Exon 6 of 7	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.32	.;.;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N;N;N
PhyloP100		-0.0090
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Benign	0.18
Sift	Benign	0.069	T;T;D
Sift4G	Benign	0.092	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.14
MutPred		0.38		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.22
MPC		0.67
ClinPred		0.70	D
GERP RS		-2.8
PromoterAI		-0.0048	Neutral
Varity_R		0.10
gMVP		0.056
Mutation Taster		=293/7	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: rs757578574; hg19: chr21-30464890;