11-75587752-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_033063.2(MAP6):c.1749T>C(p.Asp583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,716 control chromosomes in the GnomAD database, including 88,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8735 hom., cov: 31)
  • Exomes 𝑓: 0.32 (79781 hom.)
• Consequence: MAP6 NM_033063.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.795

Genes affected

MAP6 (HGNC:6868): (microtubule associated protein 6) This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-75587752-A-G is Benign according to our data. Variant chr11-75587752-A-G is described in ClinVar as [Benign]. Clinvar id is 1289911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.795 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6	NM_033063.2	c.1749T>C	p.Asp583=	synonymous_variant	4/4	ENST00000304771.8
LOC105369391	NR_145823.1	n.86+4471A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP6	ENST00000304771.8	c.1749T>C	p.Asp583=	synonymous_variant	4/4	1	NM_033063.2	A2
	ENST00000527803.1	n.86+4471A>G		intron_variant, non_coding_transcript_variant		4
MAP6	ENST00000526740.3	c.762T>C	p.Asp254=	synonymous_variant	4/4	5		A2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50179 AN: 151774 Hom.: 8704 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.369 AC: 92803 AN: 251464 Hom.: 19358 AF XY: 0.366 AC XY: 49730 AN XY: 135902

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.235

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.322 AC: 471125 AN: 1461824 Hom.: 79781 Cov.: 57 AF XY: 0.325 AC XY: 236517 AN XY: 727220

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.331 AC: 50252 AN: 151892 Hom.: 8735 Cov.: 31 AF XY: 0.340 AC XY: 25224 AN XY: 74240

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.337

Alfa AF: 0.314 Hom.: 3446

Bravo AF: 0.340

Asia WGS AF: 0.406 AC: 1410 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.21
Dann	Benign	0.81

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: rs1231128; hg19: chr11-75298797; COSMIC: COSV59076536; COSMIC: COSV59076536;