rs1180299719

Variant names:

• chr19-17725906-C-G
• rs1180299719
• NM_018174.6:c.522C>G

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.522C>G​(p.Asp174Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0850
• 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: 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=0.13331404).

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.522C>G	p.Asp174Glu	missense	Exon 5 of 7	NP_060644.4
	MAP1S	NM_001308363.2		c.444C>G	p.Asp148Glu	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.522C>G	p.Asp174Glu	missense	Exon 5 of 7	ENSP00000325313.3	Q66K74-1
	MAP1S	ENST00000594212.5	TSL:1	n.*223C>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000469123.1	M0QXE8
	MAP1S	ENST00000594212.5	TSL:1	n.*223C>G		3_prime_UTR	Exon 5 of 5	ENSP00000469123.1	M0QXE8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461492 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.085
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0090
Sift	Benign	0.21	T
Sift4G	Benign	0.74	T
Polyphen		0.0020	B
Vest4		0.038
MutPred		0.27		Loss of catalytic residue at G173 (P = 0.1486)
MVP		0.14
MPC		0.40
ClinPred		0.025	T
GERP RS		2.0
Varity_R		0.027
gMVP		0.28
Mutation Taster		=93/7	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: rs1180299719; hg19: chr19-17836715;