1-36171247-C-T

Position:

• chr1-36171247-C-T

Variant summary

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

The NM_001388490.1(MAP7D1):​c.323C>T​(p.Pro108Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP7D1 NM_001388490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

Genes affected

MAP7D1 (HGNC:25514): (MAP7 domain containing 1) Predicted to be involved in microtubule cytoskeleton organization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17381924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D1	NM_001388490.1	c.323C>T	p.Pro108Leu	missense_variant	2/17	ENST00000474796.2	NP_001375419.1
MAP7D1	NM_018067.5	c.323C>T	p.Pro108Leu	missense_variant	2/17		NP_060537.3
MAP7D1	NM_001286366.2	c.323C>T	p.Pro108Leu	missense_variant	2/18		NP_001273295.1
MAP7D1	NM_001286365.2	c.323C>T	p.Pro108Leu	missense_variant	2/16		NP_001273294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D1	ENST00000474796.2	c.323C>T	p.Pro108Leu	missense_variant	2/17	2	NM_001388490.1	ENSP00000507044.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Mar 11, 2024

The c.323C>T (p.P108L) alteration is located in exon 2 (coding exon 2) of the MAP7D1 gene. This alteration results from a C to T substitution at nucleotide position 323, causing the proline (P) at amino acid position 108 to be replaced by a leucine (L). 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	0.080
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	.;.;.;T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L;L;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D;D;D;D;N
REVEL	Benign	0.071
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		0.94, 0.78, 1.0	.;P;P;D;.
Vest4		0.36, 0.18, 0.34
MutPred		0.39		.;Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);.;
MVP		0.12
MPC		0.58
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.27

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: chr1-36636848;