Genetic Variant NM_001388490.1:c.310C>T (chr1-36171234-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001388490.1(MAP7D1):c.310C>T(p.Arg104Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,610,352 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 81 hom. )

Consequence

MAP7D1
NM_001388490.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.699

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029316545).

BP6

Variant 1-36171234-C-T is Benign according to our data. Variant chr1-36171234-C-T is described in ClinVar as [Benign]. Clinvar id is 713175.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00267 (407/152254) while in subpopulation EAS AF= 0.0443 (229/5166). AF 95% confidence interval is 0.0396. There are 6 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D1	NM_001388490.1 link	c.310C>T	p.Arg104Trp	missense_variant	Exon 2 of 17	ENST00000474796.2	NP_001375419.1
MAP7D1	NM_018067.5 link	c.310C>T	p.Arg104Trp	missense_variant	Exon 2 of 17		NP_060537.3	Q3KQU3-1
MAP7D1	NM_001286366.2 link	c.310C>T	p.Arg104Trp	missense_variant	Exon 2 of 18		NP_001273295.1	Q3KQU3-4B3KU03
MAP7D1	NM_001286365.2 link	c.310C>T	p.Arg104Trp	missense_variant	Exon 2 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.310C>T	p.Arg104Trp	missense_variant	Exon 2 of 17	2	NM_001388490.1	ENSP00000507044.1		D3DPS3

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0442

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00646

AC:

1589

AN:

245926

Hom.:

AF XY:

0.00676

AC XY:

901

AN XY:

133328

show subpopulations

Gnomad AFR exome

AF:

0.000879

Gnomad AMR exome

AF:

0.000414

Gnomad ASJ exome

AF:

0.000621

Gnomad EAS exome

AF:

0.0436

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00552

GnomAD4 exome

AF:

0.00278

AC:

4051

AN:

1458098

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2341

AN XY:

725216

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.000431

Gnomad4 ASJ exome

AF:

0.000426

Gnomad4 EAS exome

AF:

0.0386

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.00267

AC:

407

AN:

152254

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0443

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00228

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00629

AC:

764

Asia WGS

AF:

0.0320

AC:

113

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;.;.;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.95

D;D;D;D;D

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;L;L;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.099

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D;D

Polyphen

0.99, 1.0

.;D;D;D;.

Vest4

0.28, 0.31, 0.28

MVP

0.082

MPC

0.57

ClinPred

0.036

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.19

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