19-17719531-C-T

Variant names:

• chr19-17719531-C-T
• rs890539375
• NM_018174.6:c.29C>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.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000883 in 1,245,910 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.40
• Publications: 1 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=0.088858664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.29C>T	p.Ala10Val	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.29C>T	p.Ala10Val	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 9 AN: 1093818 Hom.: 0 Cov.: 30 AF XY: 0.0000116 AC XY: 6 AN XY: 516440

African (AFR) AF: 0.00 AC: 0 AN: 22942

American (AMR) AF: 0.00 AC: 0 AN: 8396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14344

East Asian (EAS) AF: 0.000151 AC: 4 AN: 26484

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3600

European-Non Finnish (NFE) AF: 0.00000326 AC: 3 AN: 919642

Other (OTH) AF: 0.0000457 AC: 2 AN: 43756

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152092 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29C>T (p.A10V) alteration is located in exon 1 (coding exon 1) of the MAP1S gene. This alteration results from a C to T substitution at nucleotide position 29, causing the alanine (A) at amino acid position 10 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PhyloP100		-1.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.029
Sift	Benign	0.27	T;.;.
Sift4G	Benign	0.18	T;T;T
Polyphen		0.031	B;.;.
Vest4		0.17
MVP		0.35
MPC		0.28
ClinPred		0.11	T
GERP RS		1.5
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.027
gMVP		0.20
Mutation Taster		=90/10	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: rs890539375; hg19: chr19-17830340; COSMIC: COSV60723630; COSMIC: COSV60723630;