19-17719534-C-T

Variant names:

• chr19-17719534-C-T
• rs1221729198
• NM_018174.6:c.32C>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.32C>T​(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,093,814 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. A11G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• 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=0.08018386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.32C>T	p.Ala11Val	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.32C>T	p.Ala11Val	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1093814 Hom.: 0 Cov.: 30 AF XY: 0.00000387 AC XY: 2 AN XY: 516438

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22950

American (AMR) AF: 0.00 AC: 0 AN: 8394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14346

East Asian (EAS) AF: 0.0000378 AC: 1 AN: 26472

South Asian (SAS) AF: 0.000102 AC: 2 AN: 19532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3604

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919574

Other (OTH) AF: 0.00 AC: 0 AN: 43764

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.7
DANN	Benign	0.89
DEOGEN2	Benign	0.062	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
PhyloP100		-1.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.71	N;.;.
REVEL	Benign	0.032
Sift	Benign	0.29	T;.;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.18	B;.;.
Vest4		0.15
MutPred		0.31		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.49
MPC		0.28
ClinPred		0.23	T
GERP RS		-5.2
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.023
gMVP		0.17
Mutation Taster		=100/0	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: rs1221729198; hg19: chr19-17830343;