Genetic Variant MAP7D1:p.Ala167Val (chr1-36172503-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388490.1(MAP7D1):c.500C>T(p.Ala167Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,448,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MAP7D1
NM_001388490.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Variant links:

Genes affected

MAP7D1 (HGNC:25514): (MAP7 domain containing 1) Predicted to be involved in microtubule cytoskeleton organization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MAP7D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D1	NM_001388490.1 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 17	ENST00000474796.2	NP_001375419.1
MAP7D1	NM_018067.5 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 17		NP_060537.3	Q3KQU3-1
MAP7D1	NM_001286366.2 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 18		NP_001273295.1	Q3KQU3-4B3KU03
MAP7D1	NM_001286365.2 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 16		NP_001273294.1	Q3KQU3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP7D1	ENST00000474796.2 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 17	2	NM_001388490.1	ENSP00000507044.1		D3DPS3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244254

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

132932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS 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:

0.00000138

AC:

AN:

1448504

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.500C>T (p.A167V) alteration is located in exon 4 (coding exon 4) of the MAP7D1 gene. This alteration results from a C to T substitution at nucleotide position 500, causing the alanine (A) at amino acid position 167 to be replaced by a valine (V). 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

.;.;.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.50

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;M;M;M;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.9

D;D;D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;.

Vest4

0.78, 0.77, 0.80

MutPred

0.35

.;Gain of methylation at K166 (P = 0.0392);Gain of methylation at K166 (P = 0.0392);Gain of methylation at K166 (P = 0.0392);.;

MVP

0.19

MPC

0.57

ClinPred

0.95

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.55

gMVP

0.34

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over