19-17719521-T-G

Variant names:

• chr19-17719521-T-G
• rs1173331214
• NM_018174.6:c.19T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018174.6(MAP1S):​c.19T>G​(p.Ser7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056352466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.19T>G	p.Ser7Ala	missense_variant	Exon 1 of 7	ENST00000324096.9	NP_060644.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP1S	ENST00000324096.9	c.19T>G	p.Ser7Ala	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1093654 Hom.: 0 Cov.: 30 AF XY: 0.00000194 AC XY: 1 AN XY: 516414

African (AFR) AF: 0.00 AC: 0 AN: 22948

American (AMR) AF: 0.00 AC: 0 AN: 8392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14340

East Asian (EAS) AF: 0.00 AC: 0 AN: 26468

South Asian (SAS) AF: 0.00 AC: 0 AN: 19528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3542

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919658

Other (OTH) AF: 0.00 AC: 0 AN: 43762

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.19
DEOGEN2	Benign	0.059	T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.15	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N;.;.
PhyloP100		-0.60
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.060	N;.;.
REVEL	Benign	0.0020
Sift	Benign	0.62	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0040	B;.;.
Vest4		0.070
MutPred		0.28		Loss of glycosylation at S7 (P = 1e-04);Loss of glycosylation at S7 (P = 1e-04);Loss of glycosylation at S7 (P = 1e-04);
MVP		0.19
MPC		0.23
ClinPred		0.11	T
GERP RS		-1.9
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.031
gMVP		0.21
Mutation Taster		=94/6	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: rs1173331214; hg19: chr19-17830330;