rs899773747

Variant names:

• chr19-17719542-A-G
• rs899773747
• NM_018174.6:c.40A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018174.6(MAP1S):​c.40A>G​(p.Ser14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 151,856 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP1S NM_018174.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052594215).

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.40A>G	p.Ser14Gly	missense	Exon 1 of 7	NP_060644.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1S	ENST00000324096.9	TSL:1 MANE Select	c.40A>G	p.Ser14Gly	missense	Exon 1 of 7	ENSP00000325313.3	Q66K74-1
	MAP1S	ENST00000594212.5	TSL:1	n.40A>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000469123.1	M0QXE8
	MAP1S	ENST00000897431.1		c.40A>G	p.Ser14Gly	missense	Exon 1 of 7	ENSP00000567490.1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151736 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000183 AC: 2 AN: 1093944 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 516450

African (AFR) AF: 0.00 AC: 0 AN: 22958

American (AMR) AF: 0.00 AC: 0 AN: 8398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14346

East Asian (EAS) AF: 0.00 AC: 0 AN: 26480

South Asian (SAS) AF: 0.00 AC: 0 AN: 19536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919592

Other (OTH) AF: 0.0000457 AC: 2 AN: 43770

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151856 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74272

African (AFR) AF: 0.000242 AC: 10 AN: 41370

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.37
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.012
Sift	Benign	0.85	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.18
MVP		0.25
MPC		0.26
ClinPred		0.037	T
GERP RS		0.016
PromoterAI		-0.034	Neutral
Varity_R		0.091
gMVP		0.46
Mutation Taster		=95/5	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: rs899773747; hg19: chr19-17830351;