3-183818091-G-T

Position:

• chr3-183818091-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024871.4(MAP6D1):​c.422C>A​(p.Thr141Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP6D1 NM_024871.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

Genes affected

MAP6D1 (HGNC:25753): (MAP6 domain containing 1) This gene encodes a protein highly similar to the mouse MAP6 domain containing 1 protein, which is related to the STOP proteins. Based on the study of the mouse protein, the encoded protein may function as a calmodulin-regulated neuronal protein that binds and stabilizes microtubules but also associates with the Golgi membranes through N-terminal palmitoylation. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35670877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6D1	NM_024871.4	c.422C>A	p.Thr141Asn	missense_variant	2/3	ENST00000318631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP6D1	ENST00000318631.8	c.422C>A	p.Thr141Asn	missense_variant	2/3	1	NM_024871.4	P1
MAP6D1	ENST00000431348.1	c.422C>A	p.Thr141Asn	missense_variant	2/3	2
MAP6D1	ENST00000445426.1	c.394C>A	p.Leu132Met	missense_variant, NMD_transcript_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 15, 2023

The c.422C>A (p.T141N) alteration is located in exon 2 (coding exon 2) of the MAP6D1 gene. This alteration results from a C to A substitution at nucleotide position 422, causing the threonine (T) at amino acid position 141 to be replaced by an asparagine (N). 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	0.22
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	0.74	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	.;N;N
REVEL	Benign	0.080
Sift	Uncertain	0.015	.;D;D
Sift4G	Benign	0.099	.;T;T
Polyphen		1.0	.;D;.
Vest4		0.48, 0.48
MutPred		0.21		.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.32
MPC		0.049
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.42

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: chr3-183535879;