chr19-17725869-C-A

Variant names:

• chr19-17725869-C-A
• rs748120717
• NM_018174.6:c.485C>A

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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. 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
• 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 -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018174.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1S	NM_018174.6	MANE Select	c.485C>A	p.Pro162Gln	missense	Exon 5 of 7	NP_060644.4
	MAP1S	NM_001308363.2		c.407C>A	p.Pro136Gln	missense	Exon 5 of 7	NP_001295292.1	Q66K74-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1S	ENST00000324096.9	TSL:1 MANE Select	c.485C>A	p.Pro162Gln	missense	Exon 5 of 7	ENSP00000325313.3	Q66K74-1
	MAP1S	ENST00000594212.5	TSL:1	n.*186C>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000469123.1	M0QXE8
	MAP1S	ENST00000594212.5	TSL:1	n.*186C>A		3_prime_UTR	Exon 5 of 5	ENSP00000469123.1	M0QXE8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.40
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.028
Sift	Benign	0.30	T
Sift4G	Benign	0.40	T
Polyphen		0.47	P
Vest4		0.16
MutPred		0.26		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
Mutation Taster		=97/3	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: rs748120717; hg19: chr19-17836678;