11-75667609-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033063.2(MAP6):c.761T>G(p.Leu254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP6 NM_033063.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10067141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6	NM_033063.2	c.761T>G	p.Leu254Arg	missense_variant	1/4	ENST00000304771.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP6	ENST00000304771.8	c.761T>G	p.Leu254Arg	missense_variant	1/4	1	NM_033063.2	A2
MAP6	ENST00000434603.2	c.761T>G	p.Leu254Arg	missense_variant	1/3	1		P2
MAP6	ENST00000526740.3	c.-83+921T>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1157838 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 560596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2021

The c.761T>G (p.L254R) alteration is located in exon 1 (coding exon 1) of the MAP6 gene. This alteration results from a T to G substitution at nucleotide position 761, causing the leucine (L) at amino acid position 254 to be replaced by an arginine (R). 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	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	6.9
Dann	Benign	0.61
DEOGEN2	Benign	0.068	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.41	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.41	N;N
REVEL	Benign	0.18
Sift	Benign	0.39	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.56	P;.
Vest4		0.25
MutPred		0.43		Gain of methylation at L254 (P = 0.0123);Gain of methylation at L254 (P = 0.0123);
MVP		0.18
MPC		2.2
ClinPred		0.22	T
GERP RS		-0.43
Varity_R		0.074
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-75378654;