Genetic Variant NM_004721.5:c.-85-10837G>A (chr3-185417660-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004721.5(MAP3K13):c.-85-10837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,611,464 control chromosomes in the GnomAD database, including 343,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26662 hom., cov: 31)

Exomes 𝑓: 0.65 ( 316774 hom. )

Consequence

MAP3K13
NM_004721.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Variant links:

Genes affected

MAP3K13 (HGNC:6852): (mitogen-activated protein kinase kinase kinase 13) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]

MAP3K13 links:

RPL4P4 (HGNC:36179): (ribosomal protein L4 pseudogene 4)

RPL4P4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K13	NM_004721.5 link	c.-85-10837G>A		intron_variant	Intron 1 of 13	ENST00000265026.8	NP_004712.1	O43283-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K13	ENST00000265026.8 link	c.-85-10837G>A		intron_variant	Intron 1 of 13	1	NM_004721.5	ENSP00000265026.3		O43283-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88036

AN:

151742

Hom.:

26646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.619

GnomAD4 exome

AF:

0.655

AC:

955695

AN:

1459606

Hom.:

316774

Cov.:

AF XY:

0.652

AC XY:

473463

AN XY:

726116

show subpopulations

Gnomad4 AFR exome

AF:

0.398

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.714

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.684

Gnomad4 OTH exome

AF:

0.635

GnomAD4 genome

AF:

0.580

AC:

88079

AN:

151858

Hom.:

26662

Cov.:

AF XY:

0.573

AC XY:

42555

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.582

Gnomad4 ASJ

AF:

0.707

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.514

Gnomad4 FIN

AF:

0.613

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.621

Alfa

AF:

0.644

Hom.:

5980

Bravo

AF:

0.573

Asia WGS

AF:

0.488

AC:

1695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.8

DANN

Benign

0.90

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over