11-75587161-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_033063.2(MAP6):c.2340G>A(p.Lys780=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00138 in 1,614,046 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00073 (14 hom.)
• Consequence: MAP6 NM_033063.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.66

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-75587161-C-T is Benign according to our data. Variant chr11-75587161-C-T is described in ClinVar as [Benign]. Clinvar id is 778541.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00757 (1152/152190) while in subpopulation AFR AF= 0.0266 (1102/41500). AF 95% confidence interval is 0.0253. There are 18 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6	NM_033063.2	c.2340G>A	p.Lys780=	synonymous_variant	4/4	ENST00000304771.8
LOC105369391	NR_145823.1	n.86+3880C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP6	ENST00000304771.8	c.2340G>A	p.Lys780=	synonymous_variant	4/4	1	NM_033063.2	A2
	ENST00000527803.1	n.86+3880C>T		intron_variant, non_coding_transcript_variant		4
MAP6	ENST00000526740.3	c.1353G>A	p.Lys451=	synonymous_variant	4/4	5		A2

Frequencies

GnomAD3 genomes AF: 0.00756 AC: 1150 AN: 152070 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00193 AC: 486 AN: 251478 Hom.: 8 AF XY: 0.00140 AC XY: 190 AN XY: 135908

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000734 AC: 1073 AN: 1461856 Hom.: 14 Cov.: 30 AF XY: 0.000594 AC XY: 432 AN XY: 727220

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00757 AC: 1152 AN: 152190 Hom.: 18 Cov.: 31 AF XY: 0.00732 AC XY: 545 AN XY: 74414

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00381 Hom.: 9

Bravo AF: 0.00887

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	6.7
Dann	Benign	0.76

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: rs151285396; hg19: chr11-75298206;