19-17725869-C-A

Variant names:

• chr19-17725869-C-A
• NM_018174.6:c.485C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018174.6(MAP1S):​c.485C>A​(p.Pro162Gln) 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. 15/21 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. P162L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058611423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6	c.485C>A	p.Pro162Gln	missense_variant	Exon 5 of 7	ENST00000324096.9	NP_060644.4
MAP1S	NM_001308363.2	c.407C>A	p.Pro136Gln	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.485C>A	p.Pro162Gln	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.21
DANN	Benign	0.75
DEOGEN2	Benign	0.0058	T;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.52	T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	.;N;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.25	.;N;.;N
REVEL	Benign	0.028
Sift	Benign	0.30	.;T;.;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.47	.;P;.;.
Vest4		0.16, 0.14
MutPred		0.26		Loss of glycosylation at P162 (P = 0.0225);Loss of glycosylation at P162 (P = 0.0225);.;.;
MVP		0.068
MPC		0.27
ClinPred		0.16	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.29

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: chr19-17836678;