19-17720965-G-T

Variant names:

• chr19-17720965-G-T
• rs114147427
• NM_018174.6:c.148G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018174.6(MAP1S):​c.148G>T​(p.Val50Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000451 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.200
• Publications: 2 publications found

Genes affected

MAP1S (HGNC:15715): (microtubule associated protein 1S) Enables DNA binding activity and cytoskeletal protein binding activity. Involved in microtubule bundle formation; neuron projection morphogenesis; and regulation of chromatin disassembly. Located in several cellular components, including microtubule cytoskeleton; nuclear lumen; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062585324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.148G>T	p.Val50Phe	missense_variant	Exon 2 of 7	ENST00000324096.9	NP_060644.4
MAP1S	NM_001308363.2	c.70G>T	p.Val24Phe	missense_variant	Exon 2 of 7		NP_001295292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP1S	ENST00000324096.9	c.148G>T	p.Val50Phe	missense_variant	Exon 2 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251474 AF XY: 0.000140

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000482 AC: 704 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.000457 AC XY: 332 AN XY: 727234

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000612 AC: 681 AN: 1111986

Other (OTH) AF: 0.000215 AC: 13 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74430

African (AFR) AF: 0.000120 AC: 5 AN: 41532

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000284 Hom.: 0

Bravo AF: 0.000208

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.148G>T (p.V50F) alteration is located in exon 2 (coding exon 2) of the MAP1S gene. This alteration results from a G to T substitution at nucleotide position 148, causing the valine (V) at amino acid position 50 to be replaced by a phenylalanine (F). 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	-0.49	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.051
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T;T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.063	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	.;L;.;.
PhyloP100		-0.20
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	.;N;.;N
REVEL	Benign	0.039
Sift	Benign	0.73	.;T;.;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.012	.;B;.;.
Vest4		0.38, 0.37
MVP		0.24
MPC		0.61
ClinPred		0.019	T
GERP RS		-7.8
Varity_R		0.032
gMVP		0.53
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs114147427; hg19: chr19-17831774;