1-36171282-G-C

Position:

• chr1-36171282-G-C

Variant summary

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

The NM_001388490.1(MAP7D1):​c.358G>C​(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MAP7D1 NM_001388490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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]

MAP7D1 (HGNC:):

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=0.094002634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D1	NM_001388490.1	c.358G>C	p.Val120Leu	missense_variant	2/17	ENST00000474796.2	NP_001375419.1
MAP7D1	NM_018067.5	c.358G>C	p.Val120Leu	missense_variant	2/17		NP_060537.3
MAP7D1	NM_001286366.2	c.358G>C	p.Val120Leu	missense_variant	2/18		NP_001273295.1
MAP7D1	NM_001286365.2	c.358G>C	p.Val120Leu	missense_variant	2/16		NP_001273294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D1	ENST00000474796.2	c.358G>C	p.Val120Leu	missense_variant	2/17	2	NM_001388490.1	ENSP00000507044.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428128 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 707556

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: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Oct 20, 2023

The c.358G>C (p.V120L) alteration is located in exon 2 (coding exon 2) of the MAP7D1 gene. This alteration results from a G to C substitution at nucleotide position 358, causing the valine (V) at amino acid position 120 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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	.;.;.;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.094	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.80	N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.36	T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T
Polyphen		0.026, 0.010, 0.18	.;B;B;B;.
Vest4		0.094, 0.12, 0.072
MutPred		0.23		.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;
MVP		0.12
MPC		0.16
ClinPred		0.12	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.081

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: rs1245331355; hg19: chr1-36636883;