NM_018174.6:c.22G>T

Variant names:

• chr19-17719524-G-T
• rs1047765544
• NM_018174.6:c.22G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018174.6(MAP1S):​c.22G>T​(p.Gly8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G8V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18655697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.22G>T	p.Gly8Trp	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.22G>T	p.Gly8Trp	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1093708 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 516428

African (AFR) AF: 0.00 AC: 0 AN: 22952

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14342

East Asian (EAS) AF: 0.00 AC: 0 AN: 26470

South Asian (SAS) AF: 0.00 AC: 0 AN: 19530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3576

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919640

Other (OTH) AF: 0.00 AC: 0 AN: 43772

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.71
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
PhyloP100		0.21
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.051
Sift	Uncertain	0.020	D;.;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.42
MutPred		0.36		Loss of disorder (P = 0.0023);Loss of disorder (P = 0.0023);Loss of disorder (P = 0.0023);
MVP		0.12
MPC		0.33
ClinPred		0.29	T
GERP RS		1.2
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.044
gMVP		0.28
Mutation Taster		=91/9	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: rs1047765544; hg19: chr19-17830333;