NM_018174.6:c.19T>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018174.6(MAP1S):​c.19T>C​(p.Ser7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,498 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. Variant has been reported in ClinVar as Likely benign (★). 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03199303).
• BP6: Variant 19-17719521-T-C is Benign according to our data. Variant chr19-17719521-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 4051157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.19T>C	p.Ser7Pro	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>C	p.Ser7Pro	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151380 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1093654 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 919658

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151498 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74090

African (AFR) AF: 0.0000242 AC: 1 AN: 41252

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67822

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 20, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.28
DEOGEN2	Benign	0.028	T;.;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.22	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.0	N;.;.
PhyloP100		-0.60
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	1.1	N;.;.
REVEL	Benign	0.0080
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.070
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.082
MPC		0.35
ClinPred		0.12	T
GERP RS		-1.9
PromoterAI		-0.11	Neutral
Varity_R		0.030
gMVP		0.22
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;