19-17725976-C-A

Variant names:

• chr19-17725976-C-A
• NM_018174.6:c.592C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018174.6(MAP1S):​c.592C>A​(p.Pro198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20122859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.592C>A	p.Pro198Thr	missense_variant	Exon 5 of 7	ENST00000324096.9	NP_060644.4
MAP1S	NM_001308363.2	c.514C>A	p.Pro172Thr	missense_variant	Exon 5 of 7		NP_001295292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP1S	ENST00000324096.9	c.592C>A	p.Pro198Thr	missense_variant	Exon 5 of 7	1	NM_018174.6	ENSP00000325313.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592C>A (p.P198T) alteration is located in exon 5 (coding exon 5) of the MAP1S gene. This alteration results from a C to A substitution at nucleotide position 592, causing the proline (P) at amino acid position 198 to be replaced by a threonine (T). 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	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N;.;N
REVEL	Benign	0.088
Sift	Benign	0.082	T;.;T
Sift4G	Benign	0.24	T;D;T
Polyphen		1.0	D;.;.
Vest4		0.19
MutPred		0.27		Loss of catalytic residue at P197 (P = 0.0365);.;.;
MVP		0.35
MPC		1.0
ClinPred		0.75	D
GERP RS		3.2
Varity_R		0.071
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17836785;