Variant 3-183825379-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024871.4(MAP6D1):c.169G>T(p.Ala57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,290,582 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

MAP6D1
NM_024871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.235

Variant links:

Genes affected

MAP6D1 (HGNC:25753): (MAP6 domain containing 1) This gene encodes a protein highly similar to the mouse MAP6 domain containing 1 protein, which is related to the STOP proteins. Based on the study of the mouse protein, the encoded protein may function as a calmodulin-regulated neuronal protein that binds and stabilizes microtubules but also associates with the Golgi membranes through N-terminal palmitoylation. [provided by RefSeq, Oct 2008]

MAP6D1 links:

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ACMG classification

Classification made for transcript

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=0.04841864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6D1	NM_024871.4 linkuse as main transcript	c.169G>T	p.Ala57Ser	missense_variant	1/3	ENST00000318631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAP6D1	ENST00000318631.8 linkuse as main transcript	c.169G>T	p.Ala57Ser	missense_variant	1/3	1	NM_024871.4	P1
MAP6D1	ENST00000431348.1 linkuse as main transcript	c.169G>T	p.Ala57Ser	missense_variant	1/3	2
MAP6D1	ENST00000445426.1 linkuse as main transcript	c.145G>T	p.Ala49Ser	missense_variant, NMD_transcript_variant	1/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000232

AC:

AN:

1290582

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

635424

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000291

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.169G>T (p.A57S) alteration is located in exon 1 (coding exon 1) of the MAP6D1 gene. This alteration results from a G to T substitution at nucleotide position 169, causing the alanine (A) at amino acid position 57 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.8

DANN

Benign

0.94

DEOGEN2

Benign

0.0093

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.96

L;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.032

Sift

Benign

0.12

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.051

B;.

Vest4

0.060

MutPred

0.16

Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);

MVP

0.13

MPC

0.0088

ClinPred

0.076

GERP RS

0.63

Varity_R

0.096

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over