6-136359992-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003980.6(MAP7):c.1843G>A(p.Ala615Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,504 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (21 hom.)
• Consequence: MAP7 NM_003980.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179

Genes affected

MAP7 (HGNC:6869): (microtubule associated protein 7) The product of this gene is a microtubule-associated protein that is predominantly expressed in cells of epithelial origin. Microtubule-associated proteins are thought to be involved in microtubule dynamics, which is essential for cell polarization and differentiation. This protein has been shown to be able to stabilize microtubules, and may serve to modulate microtubule functions. Studies of the related mouse protein also suggested an essential role in microtubule function required for spermatogenesis. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004345447).
• BP6: Variant 6-136359992-C-T is Benign according to our data. Variant chr6-136359992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP7	NM_003980.6	c.1843G>A	p.Ala615Thr	missense_variant	14/18	ENST00000354570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP7	ENST00000354570.8	c.1843G>A	p.Ala615Thr	missense_variant	14/18	1	NM_003980.6	A2

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00255 AC: 641 AN: 250918 Hom.: 7 AF XY: 0.00293 AC XY: 398 AN XY: 135618

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000900

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00888

Gnomad FIN exome AF: 0.00624

Gnomad NFE exome AF: 0.00168

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00207 AC: 3026 AN: 1461206 Hom.: 21 Cov.: 31 AF XY: 0.00232 AC XY: 1683 AN XY: 726852

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000762

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00855

Gnomad4 FIN exome AF: 0.00642

Gnomad4 NFE exome AF: 0.00162

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74478

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.000880

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00271 AC: 329

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00175

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

MAP7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.;.;.;T;.;.;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T;T;T;T;D;T;T;T;.
MetaRNN	Benign	0.0043	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.84	N;N;N;N;N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.22	T;T;T;T;T;T;T;T;T
Polyphen		0.65, 0.012	.;.;.;P;B;.;.;.;.
Vest4		0.23
MVP		0.30
MPC		0.15
ClinPred		0.028	T
GERP RS		4.0
Varity_R		0.036
gMVP		0.076

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

Other links and lift over

dbSNP: rs147645484; hg19: chr6-136681130; COSMIC: COSV63423358; COSMIC: COSV63423358;